Rapid Cycle Analysis (RCA) to Monitor the Safety of 

COVID-19 Vaccines in Near Real-Time within the Vaccine 

Safety Datalink: 

Guillain-Barré Syndrome (GBS)

Nicola Klein, MD, PhD

Kaiser Permanente Vaccine Study Center

Kaiser Permanente Northern California

Marshfield Clinic Research Institute

Vaccine Safety Datalink – Immunization Safety Office, CDC

1
Disclaimer

• The findings and conclusions in this report are those of the authors and do 

not necessarily represent the official position of the Centers for Disease 

Control and Prevention (CDC).

• Mention of a product or company name is for identification purposes only 

and does not constitute endorsement by CDC

2
• Established in 1990

• Collaborative project between CDC and 9 Integrated Health Care Organizations 

The Vaccine Safety Datalink (VSD)

3
The specific aims:

• To monitor the safety of COVID-19 vaccines weekly using prespecified outcomes of interest among VSD members. 

• To describe the uptake of COVID-19 vaccines over time among 

eligible VSD members overall and in strata by age, site, and 

race/ethnicity.

Project Period: Sept 2020 – August 2023 (3 years)

VSD Rapid Cycle Analysis

4
COVID-19 Vaccine Uptake

(Through 7/10/21)

5
VSD COVID-19 Vaccine Totals

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VSD COVID-19 Vaccine Totals

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44,188 Janssen doses 

administered to those 

aged 65 years and 

over
Primary Analyses:

Vaccinated Concurrent 

Comparisons with 

Sequential Tests 

(Data through July 10, 2021)

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Outcome events in 21-day risk interval after either dose of any mRNA vaccine

Compared with outcome events in vaccinated comparators on the same calendar days 

NE= not estimable

1Sequential test requires 1-sided p < 0.0048 for a signal. This keeps the probability of a false positive signal (due to chance alone) below 0.05 in 2 years of surveillance.

2Adjusted for VSD site, 5-year age group, sex, race/ethnicity, and calendar date. Comparison interval is 22–42 days after either dose.

3Analyses include only confirmed cases. Cases initially confirmed via “quick review” are subsequently removed if not confirmed after full chart review and adjudication.

Sequential Test1

Outcome

Event

Events

in Risk Interval

Adjusted 

Rate Ratio2

1-sided

P-value (Fisher)

'Signal’ 1-sided

p < 0.0048

Acute disseminated encephalomyelitis3 2 NE 0.660 No

Acute myocardial infarction 626 1.02 0.405 No

Appendicitis 821 0.83 0.999 No

Bell’s palsy 562 1.02 0.423 No

Cerebral venous sinus thrombosis3 8 1.61 0.386 No

Disseminated intravascular coagulation 31 0.59 0.979 No

Encephalitis / myelitis / encephalomyelitis 18 1.50 0.312 No

Guillain-Barré syndrome3 10 0.69 0.828 No

Stroke, hemorrhagic 254 0.96 0.653 No

Stroke, ischemic 1098 0.99 0.609 No

Immune thrombocytopenia 48 0.95 0.627 No

Kawasaki disease 0 0.00 0.163 No

Myocarditis / pericarditis 92 1.16 0.269 No

Seizures 298 1.01 0.472 No

Transverse myelitis3 4 3.02 0.302 No

Thrombotic thrombocytopenic purpura 6 1.67 0.379 No

Thrombosis with thrombocytopenia syndrome 76 0.88 0.780 No

Venous thromboembolism 646 1.17 0.016 No

Pulmonary embolism 519 0.99 0.555 No
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Outcome events in 21-day risk interval after Janssen vaccine

Compared with outcome events in vaccinated comparators on the same calendar days 

Sequential Test1

Outcome

Event

Events in Risk 

Interval

Adjusted 

Rate Ratio2

1-sided 

P-value (Fisher)

'Signal’ 

1-sided p < 0.0048

Acute myocardial infarction 20 1.32 0.308 No

Appendicitis 29 1.08 0.456 No

Bell’s palsy 27 1.70 0.107 No

Disseminated intravascular coagulation 2 1.14 0.692 No

Guillain-Barré syndrome3 8 1.19 0.682 No

Stroke, hemorrhagic 7 0.79 0.762 No

Stroke, ischemic 36 1.25 0.243 No

Immune thrombocytopenia 4 2.32 0.295 No

Myocarditis / pericarditis 1 3.86 0.313 No

Seizures 9 0.73 0.811 No

Thrombotic thrombocytopenic purpura 2 2.67 0.496 No

Thrombosis with thrombocytopenia syndrome3 2 NE 0.622 No

Venous thromboembolism 22 1.00 0.574 No

Pulmonary embolism 11 0.43 0.989 No

NE= not estimable

1Sequential test requires 1-sided p < 0.0048 for a signal. This keeps the probability of a false positive signal (due to chance alone) below 0.05 in 2 years of 

surveillance. 

2Adjusted for VSD site, 5-year age group, sex, race/ethnicity, and calendar date. Comparison interval is 22–42 days after either dose.

3Analyses include only confirmed cases. Cases initially confirmed via “quick review” are subsequently removed if not confirmed after full chart review and 

adjudication.
GBS Chart Review Summary

(Data through July 3, 2021)
Guillain-Barré Syndrome following any mRNA COVID-19 

Vaccine: Chart Review Summary (as of July 3, 2021) 

• 40 GBS cases identified within 1-98 days following any mRNA vaccine 

• After quick review ruled out 16/39 (1 pending), 23/39 proceeded to full review.

• 21/23 with completed full review and adjudication (2 pending).

• Adjudication confirmed 19/21 as GBS following any mRNA vaccine

• 1 case post-vaccination day 0

• 8 cases post-vaccination days 1-21

• 8 cases post-vaccination days 22-42

• 2 case post-vaccination days 43-98
Guillain-Barré Syndrome following Janssen COVID-19 

Vaccine: Chart Review Summary (as of July 3, 2021) 

• 14 GBS cases identified within 1-98 days following Janssen vaccine 

• All 14 cases were quick reviewed (2 ruled out) and 12/14 proceeded to full review.

• 10/12 with completed review and adjudication (2 pending).

• Adjudication confirmed 8/10 as GBS following Janssen vaccination

• 7 cases post-vaccination days 1-21

• 1 case post-vaccination days 22-42
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Timing of Confirmed Guillain-Barré Syndrome 0-98 days 

after COVID-19 Vaccines 
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Timing of Confirmed Guillain-Barré Syndrome 0-98 days 

after COVID-19 Vaccines 
Characteristics of Confirmed GBS Cases: 1-21 Days

mRNA (n=8) Janssen (n=7)

Age in years, median (range) 70 (44-92) 60 (53-63)

Age group

18-64 years 2 (25%) 7 (100%)

≥65 years 6 (75%) 0 (0%)

Male sex 4 (50%) 5 (71%)

Days to symptom onset from most recent dose, median (range) 2 (1-17) 8 (1-11)

Symptom onset within 21 days of most recent dose 8 (100%) 7 (100%)

Dose 1 5 (63%) 7 (100%)

Brighton Collaboration case definition level

1 0 (0%) 1 (14%)

2 4 (50%) 3 (43%)

3 1 (13%) 1 (14%)

4 3 (38%) 2 (29%)

History of COVID-19 0 (0%) 0 (0%)

Outcome at the time of chart review

Recovered without neurologic sequelae 0 (0%) 0 (0%)

Recovered with neurologic sequelae 3 (38%) 3 (43%)

Illness on-going 3 (38%) 4 (57%)

Died 2 (25%) 0 (0%)
Unadjusted Incidence Rate of Chart-Confirmed 

Guillain-Barré Syndrome 1-21 Days after Vaccination 

Vaccine Chart Confirmed 

Cases in 1-21 Day 

Risk Interval

Number of 

Doses

PersonYearsUnadjusted 

Rate per Million 

Doses1

(95% CI)

Unadjusted Rate 

per 100,000 

Person-Year1

(95% CI)

mRNA – Either Dose 8 11,715,092 673,558 0.7 (0.3 - 1.3) 1.2 (0.5 – 2.3)

Janssen 7 345,700 19,876 20.2 (8.1- 41.7) 35.2 (14.2 - 72.5)

1Incidence rates are not adjusted for age, race, sex or VSD site. 
• The VSD has not identified a signal for any outcome in the primary analyses, including GBS, 

after the mRNA or Janssen vaccines

• Analyses do not include head-to-head comparisons of Janssen with mRNA vaccines

• The chart confirmed unadjusted incidence rate of GBS during the 21 days after the Janssen 

vaccine is much higher than during the 21 days after mRNA vaccines.

• Weekly uptake of Janssen in the VSD has been minimal – ~2,500 to 11,400 doses a week.

• Continued VSD monitoring of GBS is warranted. 

• The VSD will continue to chart review every case of GBS within 1-98 days following any COVID-19 vaccination. 

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Guillain-Barré Syndrome in the VSD after COVID-19 

Vaccination: Summary
• Kaiser Permanente Northern California:

• Nicky Klein, Laurie Aukes, Berwick Chan, Bruce Fireman, Kristin Goddard, Ned Lewis, Karen Nunley, Pat Ross, 

Arnold Yee, Ousseny Zerbo, Nandini Bakshi

• Marshfield Clinic Research Institute:

• Jim Donahue, Ed Belongia, Kayla Hanson, Burney Kieke, Dave McClure, Erica Scotty, Tom Boyce

• CDC Immunization Safety Office:

• Eric Weintraub, Tat’Yana Kenigsberg, Mike McNeil, Jonathan Duffy, Frank Destefano, Tanya Myers, Tom 

Shimabukuro, Matt Oster

• VSD Sites

• HealthPartners Institute, Minneapolis, Minnesota

• Kaiser Permanente Colorado, Denver, Colorado

• Kaiser Permanente Northwest, Portland, Oregon

• Kaiser Permanente Southern California, Los Angeles, California

• Kaiser Permanente Washington, Seattle, Washington

• Denver Health, Denver, Colorado

Acknowledgements

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